The benefit-risk ratio of Rosiglitazone therapy is not defined


Diabetes is a strong, independent risk factor for cardiovascular disease, a problem which accounts for approximately 70% of all mortality in people with diabetes.
Prospective studies show that compared to their non-diabetic counterparts, the relative risk of cardiovascular mortality for men with diabetes is two to three and for women with diabetes is three to four.
The two biggest trials in type 2 diabetes, the United Kingdom Prospective Diabetes Study ( UKPDS ) and the University Group Diabetes Program ( UGDP ) study did not reveal a reduction of cardiovascular endpoints through improved metabolic control.
Theoretical benefits of the peroxisome proliferator activated receptor gamma ( PPAR-gamma ) activator Rosiglitazone ( Avandia ) on endothelial function and cardiovascular risk factors might result in fewer macrovascular disease events in people with type 2 diabetes mellitus.

Researchers assessed the effects of Rosiglitazone in the treatment of type 2 diabetes.

Studies were included in this review if they were randomised controlled trials in adult people with type 2 diabetes mellitus and had a trial duration of at least 24 weeks.

Eighteen trials which randomised 3888 people to Rosiglitazone treatment were identified.

Longest duration of therapy was four years with a median of 26 weeks.

Published studies of at least 24 weeks Rosiglitazone treatment in people with type 2 diabetes mellitus did not provide evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound.

Metabolic control measured by glycosylated haemoglobin A1c ( HbA1c ) as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs.

Occurrence of oedema was significantly raised ( OR 2.27 ).

The single large RCT ( ADOPT - A Diabetes Outcomes Progression Trial ) indicated increased cardiovascular risk.

New data on raised fracture rates in women reveal extensive action of Rosiglitazone in various body tissues.

The authors concluded, “ New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of Rosiglitazone therapy. “

Source: The Cochrane Library, 2007

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